Background & Aims
The loss‐of‐function rs72613567 T > TA‐variant in the 17β‐hydroxysteroid dehydrogenase 13 (HSD17B13) gene might protect from alcoholic and non‐alcoholic fatty liver disease (ALD/NAFLD) and associated fibrosis/cirrhosis. We investigated the impact of the T > TA‐variant on hepatic decompensation and mortality and investigated its implications on retinol and sex steroid metabolism in patients who had already developed advanced chronic liver disease (ACLD).
Methods
Retrospective analysis in prospectively characterized patients with viral hepatitis‐ and ALD/NAFLD‐induced portal hypertension (hepatic venous pressure gradient (HVPG) ≥ 6 mmHg) diagnosed at the Medical University of Vienna.
Results
Among 487 patients who were followed longitudinally, 166 (34%) were heterozygous and 24 (5%) were homozygous for the ‘protective’ TA‐allele. Patients harbouring at least one TA‐allele had a lower MELD (9 (8‐12) vs 10 (8‐13) points; P = .003) and showed a trend towards lower HVPG (16 ± 6 vs 17 ± 7 mmHg; P = .067). Interestingly, in competing risk analyses adjusted for age, HVPG and MELD, harbouring the TA‐allele was associated with numerically increased risks for mortality (adjusted subdistribution hazard ratio (aSHR): 1.3 (95% confidence interval (95% CI): 0.888‐1.91); P = .18), liver‐related death (aSHR: 1.34 (95% CI: 0.9‐1.98); P = .15) and hepatic decompensation (aSHR: 1.29 (95% CI: 0.945‐1.77); P = .11). This might be explained by trends towards worse outcomes (eg liver‐related death: aSHR: 1.64 (95% CI: 0.95‐2.84); P = .076) in patients with viral hepatitis‐induced ACLD. In a cross‐sectional analysis of 211 additional patients, serum retinol levels were comparable between HSD17B13 genotypes, but in males, serum testosterone levels numerically decreased with an increasing number of TA‐alleles.
Conclusion
In patients with viral hepatitis‐ and ALD‐induced portal hypertension, the T > TA‐variant was not protective of hepatic decompensation and mortality. Further studies should investigate the pathophysiological mechanisms underlying the effects of HSD17B13 genotype at different stages of liver disease.